Viral infection interleukins

In conclusion, IFNs have proven to be invaluable tools in the fight against chronic viral hepatitis. In these indications, their antiviral properties play a major role and it remains unclear whether their immunomodulatory properties are also important. Disappointing results obtained with purely immunomodulatory molecules, such as interleukins or Toll-like receptor agonists suggest that, if immunomodulation plays any role, potent inhibition of viral replication is also needed. The role of IFNs in the treatment of viral infections other than hepatitis B and C remains elusive. 

Multiple factors play a role in the development of AOM. Viral infection of the nasopharynx impairs eustachian tube function and causes mucosal inflammation, impairing mucociliary clearance and promoting bacterial proliferation and infection. Children are predisposed to AOM because their eustachian tubes are shorter, more flaccid, and more horizontal than adults, which make them less functional for drainage and protection of the middle ear from bacterial entry. Clinical signs and symptoms of AOM are the result of host immune response and damage to cells caused by inflammatory mediators such as tumor necrosis factor and interleukins that are released from bacteria.4... 

Anti-hepatitis B virus activity in vitro and in vivo was also found in wogonin and baicalein (Fig. 4), the major active constituents of the traditional Chinese medicine Scutellaria radix.More recently, Blach-Olszewska et al investigated the effect of baicalein and wogonin on two important mechanisms of innate immunity The secretion of cytokines, and the natural resistance of human leukocytes to viral infection. The results obtained indicate that these fiavonoids modulate cytokine production, that is they inhibit interferons-a and -y, and stimulate tumor necrosis factor-a and interleukin production. They also augment the resistance of peripheral blood leukocytes to the vesicular stomatitis virus. 

There is an extremely large number of cytokines only the most important representatives are listed opposite. The cytokines include interleukins (IL), lymphokines, monokines, chemokines, interferons (IFN), and colony-stimulating factors (CSF). Via interleukins, immune cells stimulate the proliferation and activity of other immune cells (see p. 294). Interferons are used medically in the treatment of viral infections and other diseases. 

Cytokines are a potential way to modify the immune system in several situations because of their ability to act as immunoregulatory chemicals. For example, cytokines such as interferon-alpha and interleukin-2 can be administered to treat certain forms of cancer (see Chapter 36). Likewise, certain interferons can help control viral infections, and interferon-beta may be helpful in autoimmune diseases such as multiple sclerosis (see Chapter 34). Researchers continue to investigate how immune function can be manipulated to treat various diseases, and additional immune system modulators will almost certainly be forthcoming. 

Inflammation is a common component associated with sepsis, meningitis, as well as respiratory tract, urinary tract, viral, and bacterial infections (Table 1). Bik is elevated during bacterial or viral infection. The presence of urinary Bik correlates well with standard urinalysis tests for urinary tract infections [20]. Endotoxins released from infectious pathogens induce inflammation and immune cell activation. Macrophages release interleukins and cytokines (IL-1, IL-6, IL-12, IL-15, IL-18, TNF-a) on exposure to lipo-polysaccharide (LPS) and lipoteichoic acid (LTA) endotoxins. These cytokines act as a chemotactic factors causing immune cell migration to the site of the infection followed by activation and release of proteases. Cytokines also induce increased vascular permeability in the endothelial. Bik suppresses further cytokine release by protease and intern additional migration and activation of immune cells. Additionally, a stabilization of the immune cell membrane prevents further release of proteases [4]. 

Other components of the innate response include natural killer (NK) cells and a number of cytokines. NK cells lyse certain types of tumor cells and virally infected cells and are a rich source of immune interferon (interferon-y), which stimulates macrophages and T cells hence they are thought to play an important role in host resistance to both neoplastic and viral disease. Type I interferons (interferon a and interferon P) are produced by a number of different cell types and appear very rapidly after viral infection. Type I interferons inhibit viral replication, inhibit cell proliferation, and increase the lytic potential of NK cells and therefore play a role in controlling viral and neoplastic disease. Several cytokines are important in the initiation of inflammatory responses. Those that have received the most attention include tumor necrosis factor alpha (TNFa), interleukin (IL)-1, and IL-6. There are also a number of chemotactic cytokines (including IL-8), called chemokines, which help to mobilize immune cells to the site of injury. 

Tumour necrosis factor-a (TNFa) accumulates in the brain after trauma. This cytokine is known to be an important factor in delayed CNS damage. It was found that, in addition to its anti-NMDA effect, HU-211 causes up to 90% inhibition of the TNFa surge after closed head injury in rats [195], Bacterial and viral infections of the CNS are known to cause secretion of the TNFa as well as interleukin-1 and other cytokines which are involved in the inflammatory process and may cause secondary damage. Such infections may result in high mortality. It was found that rats infected with Streptococcus pneumoniae suffered less cerebral oedema on treatment with a combination of a suitable antibiotic with HU-211 than the antibiotic alone [196],... 

Apoptosis in viral-infected cells is induced by cytotoxic T( cells bound (via both the cell surface T cell receptor and CD8 protein) to the target cell MHCI complex (which presents a virus-derived peptide). This process is assisted by interleukin-2 (IL-2) (acting via the PM IL-2 receptor on T( cells), the IL-2 having been generated by helper TH cells complexed (via both the cell surface T cell receptor and CD4 protein) to a macrophage MHCII complex... 

Depending on the site of maturation, specific surface markers, and functions, the lymphocytes are divided into T (thymus), B (bone marrow or bursa), NK, and LAK cells. T lymphocytes mature in the thymus and are involved in DTH and in anticancer and antifungal immunity. T helper (Th) and T suppressor (Ts) cells play a central role in immune regulation. The NK cells provide spontaneous and nonspecific immunity against tumor cells, virally infected, and chemically modified cells. The LAK cells are the primary blood or spleen lymphocytes that acquire the ability to kill certain tumors in vitro, when cultured with interleukin (IL)-2. They have been reported to cause regression of solid tumors when administered to experimental animals or patients with cancer and suppress the formation of metastases. 

There are a multitude of activators of NF-kB, such as viral infections, bacterial infections, radiation, interleukin (IL)-l, and tumor necrosis factor (TNF). Most of the activators of NF-kB can be blocked with the use of antioxidants (Schulze et al., 1997). Other transcription factors, such as AP-1 (Xanthoudakis et al., 1994), MAF, and NRL (Kerppola and Curran, 1994), and NF-IL6 (Hsu et al., 1994) are regulated by oxygen-dependent mechanisms that cause redox cycling of cysteinyl residues. 

As stated earlier plasma zinc concentration is low in a wide range of conditions (Halstead and Smith, 1970). One effect of stress , mediated by ACTH and cortisol, is to reduce plasma zinc. This is part of the acute phase response to accidental or surgical injury, the effect lasting for several days. Bacterial or viral infections have a similar effect. There is recent evidence that the fall in plasma zinc is part of a complex series of metabolic events induced by the humoral factors such as Interleukin 1 (Dinarello, 1982) which in turn activates interleukin-6 the active factor responsible for induction of liver... 

Reiss CS, Komatsu T, Barna M, Bi Z. Interleukin-12 promotes enhanced recovery from viral infection of neurons in the central nervous system. Annals of the New York Academy of... 

Ejmaes M. Filippi CM, Martinic MM et aL Resolution of a chronic viral infection after interleukin-10 receptor blockade. J Exp Med 2006 203(11) 2461-2472. 

Van Damme, J., Decock, B., Conings, R., Lenaerts, J. P., Opdenakker, G., and Billiau, A. (1989). The chemotactic activity for granulocytes produced by virally infected fibroblasts is identical to monocyte-derived interleukin-8. Eur. J. Immunol. 19, 1189-1194. 

The cytokines (interferon (lFN)-a,-IFN-Y, and interleukin (IL)-2) are associated with toxicides attributable to their potent stimulation of the immune system (Dranoff 2004). The most frequently reported toxicides ( flu-like symptoms, i.e., fever, headache, chills, myalgia, and fadgue, Intron-A PI 2012 Acdmmune PI 2009 Proleukin PI 2012) are similar to those that might be observed during a viral infection. However, with the doses used to treat cancer, a variety of cardiovascular toxicides have also been reported (Table 2). 

JNKs can be activated by a large range of different stimuli, including kainic acid [47], microtubule-disrupting agents [48], double-stranded ribonucleic acid (RNA) [49], viral infections [49], tumor necrosis factors, interleukins [50], osmotic stress [51], and trophic factor withdrawal [30]. JNKs have also been reported to be activated by oxidative stress, particularly that induced by ultraviolet radiation [47], hypoxia [52], ischemia [53], hydrogen peroxide [30,54], peroxynitrite [55], malondialdehyde [56], and 4-hydroxynonenal [57]. 

Cytokines and biological response modifiers represent a broad class of therapeutic agents that modify the hosts response to cancer or cancer therapies. The enormous body information about their clinical uses and their side effects is beyond the scope of this essay that can only give illustrative examples. For an up-to-date information the reader can resort to reference [5]. As many as 33 different interleukins are known and the list continues to grow IL-2 used in the treatment of kidney cancer is one example. Interferon alpha is used for chronic myelogenous leukeia, hairy cell leukaemia and Kaposi s sarcoma. Interferons are also used in the treatment of chronic infections such as viral hepatitis. Tumor necrosis factor (alpha), G/GM/M-CSF, and several other cellular factors are used in treatment of various cancers. Many of these cytokines produce serious side effects that limit their use. 

Interestingly, we have demonstrated a synergistic effect of TNFa and HDAC inhibitor on reactivation of HIV-1 expression in the latently infected U1 cell line (Quivy et al, 2002). Mechanistically, we have demonstrated that HDAC inhibitor prolongs TNFa-induced NF-kB binding to DNA (Quivy et al, 2002 Adam et al, 2003). It is important to note that an array of cytokines, including the proin-flammatory cytokines TNFa and interleukin-1 (inducers of NF-kB), are already copiously expressed in the microenvironment of the lymphoid tissues, which harbor latent viral reservoirs (Navikas et al, 1995) and could therefore, amplify the reactivation potential of HDAC inhibitors used in patients. 

Ruan, S., Tate, C., Lee, J. J., Ritter, T., Rolls, J. K. and Shellito, J. E. (2002). Local delivery of the viral interleukin-10 gene suppresses tissue inflammation in murine Pneumocystis carinii infection. Infect. Immun. 70,... 

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